DataSheet_1_Tubeimuside I improves the efficacy of a therapeutic Fusobacterium nucleatum dendritic cell-based vaccine against colorectal cancer.docx

IntroductionFusobacterium nucleatum (F. nucleatum) infection has been confirmed to be associated with the development, chemoresistance, and immune evasion of colorectal cancer (CRC). The complex relationship between the microorganism, host cells, and the immune system throughout all stages of CRC progression, which makes the development of new therapeutic methods difficult.
MethodsWe developed a new dendritic cell (DC) vaccine to investigate the antitumor efficacy of CRC immunotherapy strategies. By mediating a specific mode of interaction between the bacteria, tumor, and host, we found a new plant-derived adjuvant, tubeimuside I (TBI), which simultaneously improved the DC vaccine efficacy and inhibited the F. nucleatum infection. Encapsulating TBI in a nanoemulsion greatly improved the drug efficacy and reduced the drug dosage and administration times.
ResultsThe nanoemulsion encapsulated TBI DC vaccine exhibited an excellent antibacterial and antitumor effect and improved the survival rate of CRC mice by inhibiting tumor development and progression.
DiscussionIn this study, we provide a effective strategy for developing a DC-based vaccine against CRC and underlies the importance of further understanding the mechanism of CRC processes caused by F. nucleatum.

引言：具核梭杆菌（Fusobacterium nucleatum, F. nucleatum）感染已被证实与结直肠癌（colorectal cancer, CRC）的发生发展、化疗耐药及免疫逃逸密切相关。该微生物、宿主细胞与免疫系统在结直肠癌进展全阶段中存在的复杂相互作用，为新型治疗手段的开发带来了极大挑战。
方法：我们构建了一种新型树突状细胞（dendritic cell, DC）疫苗，以探究结直肠癌免疫治疗策略的抗肿瘤效能。通过介导细菌、肿瘤与宿主间的特异性相互作用模式，我们发现了一种新型植物来源佐剂——管柱苷I（tubeimuside I, TBI），其可同时提升树突状细胞疫苗的效能并抑制具核梭杆菌感染。将TBI包裹于纳米乳剂（nanoemulsion）中，可显著提升药物效能并降低给药剂量与给药频次。
结果：包裹于纳米乳剂中的TBI树突状细胞疫苗展现出优异的抗菌与抗肿瘤效果，通过抑制结直肠癌小鼠的肿瘤发生与进展，提升了其生存率。
讨论：本研究为开发抗结直肠癌的树突状细胞疫苗提供了一种有效策略，并凸显了进一步阐明具核梭杆菌介导结直肠癌发生发展机制的重要性。